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, Ho Dang Quy Dung1, Tran Thanh Binh1, Pham Huu Tung1, Tran Dinh Tri1, Ngo Phuong Minh Thuan1, Vu Van Khien4, Tran Thi Huyen Trang5, Bui Hoang Phuc2,6
, Evariste Tshibangu-Kabamba2
, Takashi Matsumoto2, Junko Akada2, Rumiko Suzuki2
, Tadayoshi Okimoto7, Masaaki Kodama7, Kazunari Murakami7
, Hirokazu Yano8,9,10
, Masaki Fukuyo8,9,11, Noriko Takahashi8,9,12, Mototsugu Kato13,14, Shin Nishiumi15,16, Takashi Azuma15, Yoshitoshi Ogura17,18, Tetsuya Hayashi17, Atsushi Toyoda19, Ichizo Kobayashi8,9,12,20
and Yoshio Yamaoka2,21
Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.
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